rs753855

Variant names:

• chr2-231201938-T-C
• rs753855
• NM_001352754.2:c.-42+3240T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611582.5(ARMC9):​c.-42+3240T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 150,304 control chromosomes in the GnomAD database, including 28,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (28535 hom., cov: 29)
• Consequence: ARMC9 ENST00000611582.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

Genes affected

ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]

ARMC9 Gene-Disease associations (from GenCC):

• Joubert syndrome 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611582.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC9	NM_001352754.2	MANE Select	c.-42+3240T>C		intron	N/A	NP_001339683.2
	ARMC9	NM_001271466.4		c.-42+2997T>C		intron	N/A	NP_001258395.2
	ARMC9	NM_001291656.2		c.-40+3240T>C		intron	N/A	NP_001278585.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC9	ENST00000611582.5	TSL:5 MANE Select	c.-42+3240T>C		intron	N/A	ENSP00000484804.1
	ARMC9	ENST00000349938.8	TSL:1	c.-42+3240T>C		intron	N/A	ENSP00000258417.5
	ARMC9	ENST00000683275.1		c.-42+3240T>C		intron	N/A	ENSP00000506823.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 88721 AN: 150186 Hom.: 28476 Cov.: 29

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.583

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.591 AC: 88839 AN: 150304 Hom.: 28535 Cov.: 29 AF XY: 0.589 AC XY: 43168 AN XY: 73290

African (AFR) AF: 0.858 AC: 34989 AN: 40784

American (AMR) AF: 0.475 AC: 7187 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2072 AN: 3448

East Asian (EAS) AF: 0.650 AC: 3315 AN: 5098

South Asian (SAS) AF: 0.501 AC: 2408 AN: 4802

European-Finnish (FIN) AF: 0.543 AC: 5515 AN: 10150

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31521 AN: 67586

Other (OTH) AF: 0.582 AC: 1217 AN: 2092

Alfa AF: 0.513 Hom.: 64419

Bravo AF: 0.599

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.19
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs753855; hg19: chr2-232066651;